Trifluoroacetylation and ionic hydrogenation of [2-(3-alkoxythienyl)]di(1-adamantyl)methanols

Abstract

Lithiation of 3-alkoxythiophenes followed by reaction with di(1-adamantyl) ketone leads to anti-[2-(3-alkoxythienyl)]di(1-adamantyl)methanols where the C–OH proton is intramolecularly hydrogen-bonded to the alkoxy group. The structure of the 3-methoxy derivative was confirmed by a single crystal X-ray diffraction study. Reaction of this alcohol with trifluoroacetic acid (TFA) and trifluoroacetic anhydride (TFAA) in dichloromethane gives a trifluoroacetate, the initially formed carbocation undergoing an intramolecular 1,5-hydride shift to give a carboxonium ion. However, in the absence of anhydride, trifluoroacetate is formed to the extent of about 15% only. Ionic hydrogenation with TFA and an organosilane in dichloromethane gives syn- and anti-[2-(3-methoxythienyl)]diadamantylmethanes by reduction of the carbocation, with a preference for the isomer with the Ad₂CH hydrogen close to methoxy. The corresponding 3-ethoxy compound behaves quite differently: in TFA–dichloromethane a trifluoroacetate is formed which then eliminates acetaldehyde to give anti-[2-(3-hydroxythienyl)]diadamantylmethane. In the presence of an organosilane syn- and anti-[2-(3-ethoxythienyl)]diadamantylmethanes are formed together with the 3-hydroxy derivative. Isotope labelling experiments show that the anti deoxygenation product is obtained by reduction of both the carbocation and the carboxonium ion. The 3-isopropoxy derivative reacts sluggishly with TFA and, with an organosilane, tends to give preferentially the less stable, syn deoxygenation product. The activation energies for syn to anti rotation in the [2-(3-alkoxythienyl)]diadamantylmethanes indicate significant differences in the steric effects of the alkoxy groups.